Pharmacological options for the treatment of Tourette's disorder.

Tourette's disorder is a neuropsychiatric disorder characterised clinically by motor and vocal tics, which may be associated to conductual disorders such as obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD). Although the neurochemistry of Tourette's disorder is not well known, there are some effective therapies for tics, OCD and ADHD. However, these are not devoid of adverse effects. Tics only require treatment when they interfere with the functioning of the patient. If therapy is needed, monotherapy at the minimal effective dose is desirable, but some patients may require two or more drugs. The most frequently used drugs for tics are antipsychotics (mainly pimozide and haloperidol) and clonidine. The potential usefulness of atypical antipsychotic drugs (risperidone, olanzapine, clozapine, ziprasidone) and other dopaminergic drugs (fluphenazine, sulpiride, tiapride, metoclopramide, piquindone, tetrabenazine), clonazepam, calcium channel antagonists, botulinum toxin, dopamine agonists, selegiline, and other drugs is discussed. The drugs of choice for OCD in patients with Tourette's disorder are the selective serotonin reuptake inhibitors (SSRIs), although the tricyclic antidepressant clomiplamine, which inhibits both serotonin and noradrenaline uptake, has also been found to be useful. ADHD can be treated with some psychostimulants, mainly methylphenidate, although these drugs must be used with caution. Other potentially useful drugs for the treatment of ADHD in patients with Tourette's disorder are clonidine, guanfacine, selegiline, some tricyclic antidepressants, sertraline, pimozide and clonazepam. Finally, the potential value of some nonpharmacological therapies (hypnotherapy, biofeedback, conductual therapies, electroconvulsive therapy, acupuncture and surgery) is briefly reviewed.     

Clomipramine: an antiobsessional tricyclic antidepressant

The chemistry, pharmacology, pharmacokinetics, adverse effects, and dosage of clomipramine hydrochloride are described, and clinical studies of the use of clomipramine in treating obsessive-compulsive disorder (OCD), other psychiatric conditions, and chronic pain are reviewed. Clomipramine hydrochloride, a tricyclic antidepressant, is a potent inhibitor of serotonin reuptake and may affect dopaminergic neurotransmission, suppress rapid eye movement sleep, produce changes in electrocardiograms, and elevate plasma prolactin. The drug is well absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism. Peak plasma concentrations occur three to four hours after a 150-mg oral dose. The mean elimination half-life is 39 hours. Some 66% of a dose is excreted in the urine, the remainder being eliminated in the feces. In clinical trials, clomipramine was significantly more effective than placebo, clorgiline, amitriptyline, imipramine, and doxepin in ameliorating the symptoms of OCD. Initial effects are seen at four weeks; improvement may continue for up to 18 weeks. Clomipramine may also be effective in treating panic attacks, phobias, depression, and chronic pain. The most common adverse effects of clomipramine are anticholinergic; others include nausea, seizures, and sexual difficulties. Interactions between clomipramine and barbiturates, haloperidol, monoamine oxidase inhibitors, and cigarette smoking have been documented. The usual initial adult dosage is 25-50 mg/day, titrated gradually to 250 mg/day if necessary. Clomipramine hydrochloride is a welcome new agent for the treatment of obsessive-compulsive disorder. Although its adverse-effect profile is like that of other tricyclic antidepressants, sexual dysfunction and seizures may be more frequent with this agent and limit its use.     

Predictors of response to pharmacotherapy with citalopram in obsessive-compulsive disorder.

Although serotonin reuptake inhibitors (SRIs) are the medications of choice in the treatment of obsessive-compulsive disorder (OCD), only 50-60% of patients respond to a single trial of any of these agents. Improved knowledge of the predictors of response to treatment may have important clinical implications. Data from a large randomized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response. Demographic (age, sex), clinical (OCD severity and duration, depression severity, prior treatment) and trial variables (citalopram dose, treatment duration) were included. Subjects with longer duration of OCD, more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial. In contrast, subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders. Despite greater awareness of OCD in recent years, there is evidence that the disorder continues to be underdiagnosed and undertreated. The data here emphasize the crucial importance of early diagnosis and treatment of OCD, and of pharmacotherapy with appropriate dose and duration.     

Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders

Fluvoxamine is a potent and selective serotonin reuptake inhibitor (SSRI) that has little or no effect on other monoamine reuptake mechanisms. Relative to other SSRIs, fluvoxamine is a weak inhibitor of cytochrome P450 (CYP) 2D6, a moderate inhibitor of CYP2C19 and CYP3A4 and a potent inhibitor of CYP1A2. In randomised, double-blind trials. fluvoxamine 100 to 300 mg/day for 6 to 10 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) compared with placebo. Response rates of 38 to 52% have been reported with fluvoxamine, compared with response rates of 0 to 18% with placebo. In patients with OCD, fluvoxamine had similar efficacy to that of clomipramine and, in smaller trials, the SSRIs paroxetine and citalopram and was significantly more effective than desipramine. Maintenance therapy with fluvoxamine may reduce the likelihood of relapses in up to 67% of patients with OCD. Fluvoxamine < or = 300 mg/day for 6 to 8 weeks was as effective as imipramine in patients with panic disorder, and significantly more effective than placebo. In addition, treatment with fluvoxamine < or = 300 mg/day for > or = 8 weeks improved symptoms of social phobia (social anxiety disorder), post-traumatic stress disorder (PTSD), pathological gambling, compulsive buying, trichotillomania, kleptomania, body dysmorphic disorder, eating disorders and autistic disorder. Large trials comparing the efficacy of fluvoxamine and other SSRIs in patients with anxiety disorders are warranted. Fluvoxamine is generally well tolerated; in postmarketing studies, nausea was the only adverse event occurring in >10% of patients with less commonly reported events including somnolence, asthenia, headache, dry mouth and insomnia. Fluvoxamine is associated with a low risk of suicidal behaviour, sexual dysfunction and withdrawal syndrome. Fewer anticholinergic or cardiovascular events are associated with fluvoxamine than tricyclic antidepressants. Although comparative data are lacking, the tolerability profile of fluvoxamine appears to be broadly similar to those of other SSRIs. CONCLUSION: Fluvoxamine has demonstrated short term efficacy in the treatment of OCD, panic disorder, social phobia, PTSD and in a range of obsessive-compulsive spectrum disorders. The drug is as effective as clomipramine in patients with OCD but appears to have a better tolerability profile. On the basis of current treatment guidelines, fluvoxamine, like other SSRIs, is recommended as first-line treatment for a number of anxiety disorders. It appears to offer some pharmacokinetic advantages and a different drug interaction profile to the other SSRIs with a broadly similar spectrum of adverse events. However, direct comparisons are required to assess the relative efficacy and tolerability of the different agents of this drug class.     

N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder

Rationale Dysfunction of glutamatergic neurotransmission has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD) and recent clinical reports suggest that some glutamate modulating agents are efficacious in the treatment of this disorder. N-acetylcysteine (NAC) is a readily available amino acid compound that is thought to attenuate glutamatergic neurotransmission. NAC may be useful in treating psychiatric disorders involving glutamatergic dysfunction such as OCD. Objectives To examine the efficacy of augmentation with NAC in a patient with serotonin reuptake inhibitor (SRI)-refractory OCD. Methods A patient with SRI-refractory OCD was treated with an off-label use of NAC augmentation of fluvoxamine over several weeks. Results NAC augmentation of fluvoxamine resulted in a marked decrease in Yale-Brown Obsessive Compulsive Scale (Y-BBOCS) score and a clinically significant improvement in OCD symptoms. Conclusions NAC augmentation was effective in treating SRI-refractory OCD in this single case. Further research is warranted to investigate the use of NAC and other glutamate modulating agents in the treatment of OCD.     

A controlled comparison of adjuvant lithium carbonate or thyroid hormone in clomipramine-treated patients with obsessive-compulsive disorder

In this study, 16 patients with obsessive-compulsive disorder (OCD) who had partially improved during at least 6 months of treatment with clomipramine were sequentially treated with triiodothyronine and lithium carbonate in an 8-week double-blind cross-over study. Both triiodothyronine and lithium carbonate have been reported to be efficacious in open trials as adjunctive agents when combined with tricyclics in the treatment of OCD and depressed patients. However, in our controlled study, OCD and depressive symptoms, as assessed by standardized rating scales in the patient group as a whole, did not significantly change after either adjuvant treatment. Further analysis on an individual patient basis revealed that neither adjuvant medication was associated with a clinically meaningful change (greater than 25%) in OCD symptoms. However, lithium, but not triiodothyronine, adjuvant therapy was associated with a 25% or greater reduction in depression scores in 44% of the patients. This controlled study lends further support to the contention that OCD may represent a disorder with characteristics distinct from affective disorders.     

Pharmacological and clinical aspects of fluvoxamine (Depromel), the first selective serotonin reuptake inhibitor approved for clinical use employed in Japan

Fluvoxamine (Depromel), a selective serotonin reuptake inhibitor (SSRI), was launched in May 1999 in Japan with more than 10 years' delay from the marketing in Europe and the United States. Fluvoxamine has been approved in about 80 countries as the indication to "depression" since 1983. As the indication to obsessive-compulsive disorder (OCD), fluvoxamine was first approved in the United States in 1994 and then in about 30 countries. Efficacy of the drug on "depression and depressed state" was found to be comparable to traditional tricyclic antidepressants (TCAs) by the clinical studies in Japan. Indication to OCD was first approved for fluvoxamine in Japan. The antidepressant and the anti-OCD action are considered the result of the serotonin reuptake inhibition at the serotonergic neurons. Fluvoxamine has little affinity for muscarinic, adrenergic alpha 1- and histamine H1-receptors, which TCAs have. Therefore, fluvoxamine possesses less side effects such as dry mouse, disuria, dizziness, orthostatic hypotension and drowsiness, etc.; and it is useful for elderly patients and long-term treatments for depression and OCD.     

A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder.

In this study, 14 patients with obsessive-compulsive disorder (OCD) who had received at least 3 months of treatment with clomipramine were treated with the anxiolytic agent buspirone in a 10-week, double-blind study. Before the addition of buspirone, these patients as a group had shown a partial but incomplete reduction (averaging 28%) in OCD symptoms during clomipramine treatment alone. Because buspirone has been reported to be efficacious as a sole agent and as an adjunct agent in combination with fluoxetine in patients with OCD, we were interested in assessing whether buspirone added to clomipramine treatment would be associated with further significant reductions in OCD or depressive symptoms. Although adjuvant buspirone treatment was well tolerated in most subjects, mean OCD and depressive symptoms, as evaluated by standardized rating scales, did not significantly change from baseline scores achieved on clomipramine treatment alone, either after the addition of placebo for 2 weeks or buspirone (57 +/- 7 mg/day) for an additional 10 weeks. However on an individual basis, 4 (29%) of the 14 patients did have an additional 25% reduction in OCD symptoms after adjuvant buspirone treatment. This double-blind study suggests that adjunctive buspirone therapy is not generally associated with significant further clinical improvement in OCD or depressive symptoms compared with clomipramine monotherapy, but that there may be a subgroup of patients who do benefit from adjuvant buspirone therapy.     

Clomipramine versus fluoxetine in obsessive-compulsive disorder: a retrospective comparison of side effects and efficacy

Since it will be some time until data will be available comparing clomipramine and fluoxetine for the treatment of patients with obsessive-compulsive disorder (OCD), a meta-analysis of previous studies was performed in an attempt to gain some information about comparable efficacy and side effects of these two commonly used agents. In 31 OCD patients receiving clomipramine in a controlled trial and 72 OCD patients receiving fluoxetine openly, both drugs appeared effective, with clomipramine having a somewhat larger effect than fluoxetine. Different side effect profiles may have a bearing on patient selection.     

Current concepts in the pharmacological treatment of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and often disabling disease. OCD is characterised by intrusive, unwanted and persistently recurring mental events (obsessions) that usually evoke discomfort or anxiety, and/or repetitive ritualistic behaviours (compulsions) that are aimed at reducing discomfort and anxiety. However, the compulsions succeed only in achieving transient relief, followed by a growing sense of pressure. 10 years ago, OCD was considered a rare and treatment-refractory disorder. Recent well designed studies document a lifetime prevalence rate for OCD of more than 2% in the general population. The outlook for patients with OCD has changed in the last decade, with many well controlled studies showing that OCD patients respond to specific behavioural and pharmacological treatments. The specific form of behavioural therapy is in vivo exposure coupled with response prevention. Only serotonin reuptake inhibitors, such as clomipramine, fluoxetine and fluvoxamine, are effective in the treatment of both depressed and not depressed OCD patients. Fluoxetine and fluvoxamine lack the anticholinergic side effects of clomipramine and, thus, provide an alternative treatment for patients who cannot tolerate clomipramine. Other nonserotonergic antidepressants (tricyclics and monoamine oxidase inhibitors) and anxiolytic agents have not been found to be consistently effective in this disorder. Insufficient data on the efficacy of neuroleptics and their potentially irreversible side effects limit their use in OCD patients. Behavioural and the pharmacological treatment are complementary, and a combination of the 2 therapies is apparently more effective than either modality alone.     

Nontraditional analgesics for the management of postherpetic neuralgia

The pathogenesis and clinical manifestations of herpes zoster and postherpetic neuralgia and the use of nontraditional analgesics in the management of postherpetic neuralgia are reviewed. Herpes zoster represents the reactivation in an immunocompromised host of dormant varicella-zoster virus (Herpesvirus varicellae) contracted during a previous episode of chickenpox. Fever, neuralgia, and paresthesia occur four to five days before skin lesions develop. Acute herpes zoster pain usually does not last more than two weeks after all skin lesions have healed. Postherpetic neuralgia is defined as pain that persists in the affected dermatomes after the disappearance of all skin crusts. The neuralgia can vary from "lightninglike" stabbing pain to constant, burning pain with hyperesthesia; it can persist for years and is often refractory to traditional analgesic therapy. A number of nontraditional analgesic agents have been used in the management of postherpetic neuralgia. Tricyclic antidepressants, especially amitriptyline, have been used alone and in combination with phenothiazines or anticonvulsants (carbamazepine, phenytoin, valproate sodium), with good results. The effectiveness of phenothiazines or anticonvulsants as sole therapeutic agents has not been demonstrated. Although the intralesional administration of corticosteroids appears to be beneficial, considerable fear about the potential for these agents to precipitate widespread viral dissemination exists. Positive results have been reported with levodopa, amantadine, and interferon, but the role of these agents in the prevention of postherpetic neuralgia remains unclear. Nontraditional analgesic agents are useful in the management of postherpetic neuralgia, but patients must be selected and monitored appropriately. A tricyclic antidepressant (especially amitriptyline) is a reasonable first choice.     

Current and up-and-coming pharmacotherapy for obsessive-compulsive disorder in adults

ABSTRACT

Introduction: Only 40–60% of obsessive-compulsive patients respond to first line treatments, such as selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy. Several second-line treatments have been investigated in the last two decades, and most of them seem to work, at least in a subset of patients. However, since there is still a lack of treatment predictors, the treatment of obsessive-compulsive disorder (OCD) is still empirical and non-evidence based.

Areas covered: In this paper, we review current and up-and-coming pharmacotherapy for OCD in adults, focusing on two emerging fields of research, inflammation and glutamate systems, since they have attracted the greatest attention in recent years in OCD pharmacological research.

Expert opinion: Most of the investigated second-line agents seem to work at least in a subset of patients with OCD. These results raise an open question: what works for who? In our opinion, this question should be answered in a precision medicine perspective or, in other words, individualizing diagnostic processes and treatment approaches. In a precision medicine approach, OCD treatment should be sub-type specific, phase specific, multimodal and sequential, and, more importantly, dimensional.     

Loeffler's syndrome: an uncommon adverse reaction to imipramine

Loeffler's syndrome (simple pulmonary eosinophilia) is an uncommon side effect of tricyclic antidepressants. It is an allergic reaction characterised by diffuse eosinophilic lung infiltrates and a peripheral blood eosinophilia. It is often asymptomatic, but can also present with mild to moderate pulmonary symptoms. Although it has been only rarely reported with imipramine and desmethylimipramine, it may be a more common side effect to tricyclic antidepressants than has been previously recognized.     

Pasteur Euroconference on future therapies for an anxious world

The aim of this meeting was to explore the molecular targets for tomorrow's drugs with a group of European and North American speakers from the pharmaceutical industry and academia presenting both data and ideas. Several speakers considered 5-hydroxytryptamine(1B/D) (5-HT(1B/D)) receptor antagonists to be a promising target for the treatment of obsessive compulsive disorders (OCD). 5-HT moduline, a peptide modulator of the 5-HT(1B/D) receptor, presents a potentially subtle way of intervention. No clinical data are as yet available on 5-HT(1B/D) receptor antagonists. The paradox of agonists, partial agonists and antagonists at the 5-HT(1A) receptor (all having anxiolytic activity in animal models) was discussed. Although the 5-HT(1A) agonists tested in clinical trials to date have been disappointing, the clinical potential of 5-HT(1A) antagonists still has to be evaluated. Similarly, both agonists and antagonists at the 5-HT(2C) receptor have been shown to be active in animal models of anxiety. It seems, however, that 5-HT(2C) agonists may have a therapeutic potential in panic disorders and OCD, while the antagonists may be more appropriate in generalised anxiety. Cholecystokinin (CCK) has been shown to be implicated in panic attacks which can be induced by agonists at the CCK-B subtype. CCK-B antagonists are thus potential antipanic agents although this has not yet been confirmed by clinical trials. Finally, inhibition of glutamatergic neurotransmission produces anxiolytic effects in a wide-range of animal models and the new antagonists at the metabotropic glutamate receptors may have potential as anti-anxiety agents. This report focuses on the presentations that addressed novel drug candidates or potential new drug targets.     

Pasteur Euroconference on Future Therapies for an Anxious World

The aim of this meeting was to explore the molecular targets for tomorrow’s drugs with a group of European and North American speakers from the pharmaceutical industry and academia presenting both data and ideas. Several speakers considered 5-hydroxytryptamine_1B/D (5-HT_1B/D) receptor antagonists to be a promising target for the treatment of obsessive compulsive disorders (OCD). 5-HT moduline, a peptide modulator of the 5-HT_1B/D receptor, presents a potentially subtle way of intervention. No clinical data are as yet available on 5-HT_1B/D receptor antagonists. The paradox of agonists, partial agonists and antagonists at the 5-HT_1A receptor (all having anxiolytic activity in animal models) was discussed. Although the 5-HT_1A agonists tested in clinical trials to date have been disappointing, the clinical potential of 5-HT_1A antagonists still has to be evaluated. Similarly, both agonists and antagonists at the 5-HT_2C receptor have been shown to be active in animal models of anxiety. It seems, however, that 5-HT_2C agonists may have a therapeutic potential in panic disorders and OCD, while the antagonists may be more appropriate in generalised anxiety. Cholecystokinin (CCK) has been shown to be implicated in panic attacks which can be induced by agonists at the CCK-B subtype. CCK-B antagonists are thus potential antipanic agents although this has not yet been confirmed by clinical trials. Finally, inhibition of glutamatergic neurotransmission produces anxiolytic effects in a wide-range of animal models and the new antagonists at the metabotropic glutamate receptors may have potential as anti-anxiety agents. This report focuses on the presentations that addressed novel drug candidates or potential new drug targets.     

Serotonergic drugs in the treatment of depressive and anxiety disorders

Serotonergic dysfunction has been implicated in the aetiology of several psychiatric conditions, including depressive and anxiety disorders. Much of the evidence for the role of serotonin (5-HT) in these disorders comes from treatment studies with serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs), 5-HT(1A) agonists and 5-HT antagonists. This review considers the place of these drugs in the treatment of panic disorder, obsessive-compulsive disorder (OCD), social phobia, and generalized anxiety disorder (GAD). Among these agents, the SSRIs stand out with proven efficacy in the treatment of a spectrum of disorders, such as depression, panic disorder, OCD and social phobia. They may also be a suitable treatment for GAD. 5-HT(1A) agonists have been used extensively for the treatment of depression and GAD but evidence of their efficacy in other anxiety disorders is equivocal. 5-HT antagonists are the least well studied of these agents: while they may have activity in depression, their efficacy has not been fully investigated in anxiety disorders. However, preliminary reports suggest that they may be useful as adjuvants to SSRIs in treatment-refractory OCD. The high incidence of comorbidity amongst psychiatric disorders means that pharmacotherapy that is effective against a range of disorders, such as the SSRIs, is of considerable use to clinicians. Future research into the biological mechanisms underlying such disorders is likely to further enhance pharmacotherapy. Copyright 2000 John Wiley & Sons, Ltd.     

Quetiapine and ziprasidone as adjuncts in treatment-resistant obsessive-compulsive disorder: a retrospective comparative study

BACKGROUND AND OBJECTIVE: While serotonin reuptake inhibitors (SRIs) are first-line pharmacological agents in the treatment of obsessive-compulsive disorder (OCD), 40-60% of patients with the disorder do not respond to these agents. This suggests that other neurotransmitters may play a role in OCD. In this regard, there has been particular interest in the dopaminergic system, with various antipsychotic drugs having been used as adjunctive therapy for refractory OCD. The aim of this study was to compare the efficacy of quetiapine and ziprasidone as adjuncts for treatment-resistant OCD. METHODS: A total of 24 OCD patients treated with either quetiapine (n = 15) or ziprasidone (n = 9) as adjunctive therapy to high-dose SRI treatment were included in this retrospective evaluation. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Clinical Global Impression (CGI) scale scores were used to evaluate baseline clinical status and clinical improvement at 1, 2, 3 and 6 months of follow-up. RESULTS: Clinical improvement was established in 80% of the quetiapine group and in 44.4% of the ziprasidone group with an overall mean improvement rate on the Y-BOCS scale of 66.7%. Both Y-BOCS and CGI mean scores were higher in the ziprasidone group at 2, 3 and 6 months follow-up than in the quetiapine group. CONCLUSIONS: In the first reported study of its role in this setting, ziprasidone was found to be less effective than quetiapine in the treatment of refractory OCD.     

Parental obsessive-compulsive disorder as a prognostic factor in a year long fluvoxamine treatment in childhood and adolescent obsessive-compulsive disorder

Interest in the treatment of pediatric obsessive-compulsive disorder (OCD) has increased as our knowledge of adult OCD has expanded. Although adults are still the majority of patients, children and adolescents with OCD are being identified and treated more frequently. As this population is better identified, prognostic factors need to be addressed to improve treatment outcome. The purpose of this study was to determine the role of family psychiatric pathology in fluvoxamine treatment outcome. Eleven children and adolescents with OCD and one of their parents participated in the study. Four parents were diagnosed with OCD, six had an Axis I diagnosis other than OCD, and one had no mental disorder [Structured Clinical Interview for the DSM-Non-Patient edition (SCID-NP)]. Each patient received fluvoxamine for 58 weeks. Dependent measures included the Children Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the NIMH-Global Obsessive Compulsive Scale (NIMH-GOCS) and the Clinical Global Impression (CGI). Based on CY-BOCS, CGI and NIMH-GOCS scores, patients with parents who have OCD showed a clinically and statistically significant reduction in symptoms from pre- to post-treatment. Patients whose parents did not have OCD also improved. However, the improvement was statistically but not clinically significant. The presence of OCD in one parent seems to modify a child's response to medication. The results suggest that family psychopathology, specifically presence of OCD, may contribute to treatment efficacy. Further research is suggested in this area.     

Treatment strategies of obsessive-compulsive disorder and panic disorder/agoraphobia

Anxiety disorders represent the most prevalent psychiatric disorders. In addition, a considerable burden is associated with them, not only for individual sufferers, but also for the health care system. However, many patients who might benefit from treatment are not diagnosed or treated. This may partly be due to lack of awareness of the anxiety disorders by primary care practitioners and by the sufferers themselves. In addition, the stigma still associated with psychiatric disorders and lack of confidence in psychiatric treatments are factors leading to no/under recognition and treatment, or the use of unnecessary or inappropriate treatments. This paper aims to provide a comprehensive review of recommendations for the pharmacological treatment of two common anxiety disorders, in particular obsessive-compulsive disorder (OCD) and panic disorder (PD). The first-line treatments of OCD include medium-high doses of selective serotonin reuptake inhibitors (SSRIs) and clomipramine, a tricyclic (TCA) antidepressant with prevalent serotonergic activity. The recommended drugs for PD include SSRIs, TCAs and serotonin-norepinephrine reuptake inhibitors (SNRIs); in treatment-resistant cases, benzodiazepines like alprazolam may be used in patients with no history of addiction and tolerance. Other treatment options include irreversible and reversible monoamine-oxidase inhibitors, hydroxyzine, and others. Besides pharmacological treatments, some psychological strategies have been shown to be effective, in particular, cognitive behavior therapy (CBT) and other variants of behavior therapy that have been sufficiently investigated in controlled studies, and, therefore, will be reviewed herein.     

Loxapine: a review of its pharmacological properties and therapeutic efficacy as an antipsychotic agent.

Loxapine is a dibenzoxazepine, tricyclic compound recommended for the treatment of acute and chronic schizophrenia. In its therapeutic effectiveness and profile and incidence of side-effects, loxapine closely resembles the traditional antipsychotic agents. Although loxapine has tended to be less effective than some standard antipsychotic drugs in a few short-term (3 to 4 weeks) studies, it has been superior to a placebo and about as effective as chlorpromazine, haloperidol, trifluoperazine or thiothixene when evaluated after 4 to 12 weeks. Like the phenothiazine (e.g. chlorpromazine) and butyrophenone (e.g. haloperidol) antipsychotic agents, loxapine causes a high incidence of extrapyramidal reactions. Sedation occurs frequently, especially during early stages of treatment. Other, less common side-effects such as anticholinergic effects (dry mouth, blurred vision, etc.), hypotension, tachycardia and precipitation of epileptic seizures, which occur with the older antipsychotic drugs, have also been reported with loxapine.